Conventionally, it has been known that a connective tissue of an animal contains, as a main component thereof, collagen, hyaluronic acid, elastin, chondroitin sulfate, heparan sulfate, dermatan sulfate, laminin or the like. Among them, collagen and hyaluronic acid play an important role in a connective tissue as described later.
In other words, collagen is a main protein constituting a connective tissue of an animal, and particularly, collagen occupies nearly 30% of a total protein of a human body. Since the main function of collagen lies in formation of a skeletal structure of a living tissue, collagen is widely distributed in skin, cartilage tissues, a cornea, the heart, the liver or the like as a main component constituting a skeletal structure of a tissue form of an animal. Since collagen specifically acts on adhesion of various kinds of cells, and differentiation or proliferation of a cell, and also has a role as a regulatory factor for cell function, decrease in collagen may cause various diseases, such as corneal disorders such as corneal ulcer, articular disorders such as rheumatism, arthritis, degenerative arthritis and osteoarthritis, and inflammatory diseases in some cases.
In a skin dermis extracellular matrix, formation of a network bundle from a collagen fiber maintains a tissue form. When a collagen fiber is matured and proliferated to proceed with cross-link formation, to give a thick and straight collagen fiber bundle, which in turn gives appropriate skin tautness in a young skin. However, in an aged skin, with the lowering of an activity (e.g. an activity for collagen production and the like) of fibroblast, since a collagen fiber in a dermis extracellular matrix is remarkably decreased and an abnormal aging cross-link is formed, skin becomes rigid, and original skin tautness rich in elasticity is undesirably lost. As a result, wrinkles and sagging are formed in the skin. Change in a collagen fiber bundle structure of a hairless mouse by photoaging has been studied in detail (see Fragrance Journal, 4, 36-37, 1998). The results show that in a hairless mouse irradiated with UVB, wrinkles are formed, a collagen fiber bundle structure is broken down, and skin elasticity is reduced, so as to match the formation of the wrinkles. In addition, it has also been known that collagen is excellent in the moisture retaining function.
In order to improve the state caused by decrease in collagen, various substances for enhancing collagen synthesis have been found. For example, retinoic acid (see, for example, R. Marks et al., British Journal of Dermatology, 122, 91-98, 1990), a preparation containing three kinds of amino acids consisting of glycine, proline and alanine (see, for example, Japanese Patent Laid-Open No. Hei 7-194375), a plant extract from licorice, mulberry bark, aloe, Equisetam arvense, Lonicerae flos, cork tree bark, leaf of Artemisia princeps, gentian or the like (see for example, Japanese Patent Laid-Open No. 2001-206835), TGF-b, ascorbic acids and the like have been known. In addition, as another substance for enhancing collagen synthesis, a peptide consisting of 182nd to 241st amino acid residues of type I procollagen (see, for example, K. Katayama et al., Biochemistry, 30, 7097-7104, 1991), and a Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 21) peptide selected from the above-mentioned peptide consisting of 182nd to 241st amino acid residues of type I procollagen (see, for example, K. Katayama et al., J. Biol. Chem., 268(14), 9941-9944, 1990) have been known.
On the other hand, hyaluronic acid is a kind of acidic mucopolysaccharides, which is present in skin, cartilage, a joint fluid, an umbilical cord, an ocular vitreous body, or other connective tissues. Inter alia, in skin epidermis, there have been known that hyaluronic acid is widely distributed from a basal layer to a granular layer, and that hyaluronic acid supports a structure of an epidermis extracellular space, and is involved in transportation of a substance such as a nutrient or a waste from an epidermal basal layer to a horny cell layer, and serves as a trigger for enhancing turnover of an epidermal cell. In addition, it has also been known that hyaluronic acid has a strong water-retaining action that about 6 L of water can be retained in only 1 g of hyaluronic acid, and that by this action, hyaluronic acid plays a role in retaining moisture in an intercellular space. It has been known that hyaluronic acid is gradually decreased with aging, and this decrease also is one cause for aging of a skin such as forming wrinkles and sagging of skin, the lowering in elasticity of skin and skin tautness, skin dryness, or skin roughness as in the case of collagen. However, hyaluronic acid is a polymer compound, so that it is not easy to supply the hyaluronic acid to an epidermis from the outside of the skin and in order to supply hyaluronic acid to a portion such as between epidermal cells, it is important to enhance biosynthesis of hyaluronic acid within a living body.
In order to improve the state caused by a decrease in hyaluronic acid, various substances for enhancing hyaluronic acid synthesis have been found. For example, an aloe extract, an okra extract, a water-soluble β-1,3-glucan derivative, an yeast extract (Japanese Patent Laid-Open No. 2004-051533), an extract of a sea alga belonging to the genus Callophyllis in the family Kallymeniaceae, (Japanese Patent Laid-Open No. 2000-136147), a lavender extract (Japanese Patent Laid-Open No. Hei 10-182402), and an extract of a sea alga belonging to the genus Durvillea in the family Durvilleaceae (Japanese Patent Laid-Open No. Hei 09-176036) have been known.